1. Technical Field
The present disclosure relates to compositions and methods for improving vascular health. Specifically, the present disclosure relates to synergistic compositions and methods of treating endothelial glycocalyx.
2. Relevant Technology
The glycocalyx is a polysaccharide-rich layer found on the luminal surface of epithelial cells lining mammalian organs and tissues. In the case of the vascular system, the glycocalyx coats the luminal surface of the endothelium—the vascular endothelial cells lining the inside of all blood vessels. As depicted in FIG. 1, for example, in vivo imaging of a capillary blood vessel illustrates that red blood cells (RBC) flowing through the lumen of the blood vessel do not contact the vessel wall endothelium. FIG. 2 illustrates a detailed view of an electron micrograph image capturing a cross-section of a capillary. As depicted, the dense glycocalyx extends from the endothelial cells into the lumen of the blood vessel, forming a micro-thin, gel-like layer.
Until recently, the role of the endothelial glycocalyx had not been well understood. In theory, however, the glycocalyx may act as a protective barrier for the vascular wall or may provide a micro-environment for certain vascular processes. Molecules that associate with the glycocalyx may dynamically interact with the endothelial cells to play a role in orchestrating a variety of functions in the circulatory system. The circulatory system, in turn, plays a role in regulating adequate organ perfusion and in the distribution and exchange of oxygen, nutrients, and hormones within tissues. Furthermore, microcirculation controls tissue hydration and organizes the defense against pathogens.
As illustrated in FIGS. 2A-2D, endothelial glycocalyx can be observed in varying degrees of thickness and/or density; indications of the “health” of the endothelial glycocalyx. FIG. 2A, for example, depicts an electron micrograph image of a “healthy” endothelial glycocalyx, while FIG. 2D depicts a severely damaged or perturbed “unhealthy” endothelial glycocalyx. FIG. 2B and FIG. 2C illustrate, respectively, intermediate states of endothelial glycocalyx health (e.g., as indicated visually by the thickness and/or density thereof). The cause(s) of such structural damage and/or depletion of the endothelial glycocalyx remain largely unknown.
Impairment of the glycocalyx barrier through structural damage or depletion, functional deficiency, or other mechanism may be a contributing cause of microvascular endothelial dysfunction, including inflammatory and coagulatory endothelial activation, vascular leakage of fluid, proteins, and other substances (e.g., cholesterol), failure to properly modulate perfused blood vessel density, and other deleterious conditions, leading to general and specific negative vascular health indicators. As depicted in FIG. 3B, for example, an unhealthy endothelial glycocalyx is associated with a “leaky” endothelium, as evidenced by (1) the presence (or “leakage”) of cholesterol (or other substances, such as fluids, proteins, etc.) in (or into) the subendothelial space, and (2) a constricted lumen, which may reduce blood flow or perfusion into distal capillaries, muscles, organs, etc., increase blood pressure, and so forth. As illustrated in FIG. 3A, however, a healthy (thick and/or dense) endothelial glycocalyx is associated with a well-formed endothelium and healthy blood vessel structural configuration.
Accordingly, there is a need for products and processes for treating (e.g., supporting and/or maintaining) endothelial glycocalyx.